Mitogenic,immunoadjuvancy, and genetic studies on fatty acyl maltose

Summary Three synthetic glycolipids, maltose tetrapalmitate (MTP), maltose hexastearate (MHS), and maltose hexalinoleate (MHL) prepared as nontoxic lipid A analogs, and Escherichia coli lipopolysaccharide (LPS) were assayed for their mitogenic activity using spleen lymphocytes in nine inbred mouse strains and three F1 hybrids. The MTP and LPS were also assayed for their ability to enhance plaque-forming cell (PFC) responses using sheep red blood cells as the antigen in th same inbred mouse strains and F1 hybrids, The mitogenic activity of synthetic glycolipids was several fold lower than that of LPS and MHL was inferior to MTP and MHS. DBA/2J was the most responsive strain for MTP and DBA/1J and C3H/HeJ the least. The mitogenic activity of MTP was generally in agreement with the PFC response stimulation by it. Lowdose cyclophosphamide treatment of mice synergized MTP for PFC response augmentation. Genetic studies on MTP mitogenicity revealed that 90% of responder DBA/2J X nonresponder C3H/HeJ F1 hybrids had intermediate mitogenic activity. Among F2, 73% had intermediate-high activity and 27% were nonmitogenic. Among F1 X C3H/HeJ backcrosses 11% had high, 56% intermediate, and 33% had no mitogenic activity, whereas, for the F1 X DBA/2J backcross, 14% had high, 36% intermediate, and 50% low or negligible activity. The data favored a single gene for MTP activation of immune cells.This work was supported, in part, by a grant from the National Cancer Institute of Canada, and by grant from the Cancer Research Society Inc.     

Effect of methionine-sulfoximine on nitrate uptake and photosynthesis in the cyanobacteriumAnabaena doliolum Bharadwaja

l-Methionine-dl-sulfoximine (MSX) stimulated nitrate uptake but inhibited¹⁴CO₂ fixation and O₂ evolution inAnabaena doliolum. Nitrate uptake was inhibited by ammonium (NH ₄ ⁺ ) in the absence of MSX, but not in the presence of MSX. Glutamine or a derivative of it appears to be the actual negative effector of nitrate utilization. In presence of nitrate, MSX-treated cells ofA. doliolum evolve more O₂ than do untreated cells. Our results suggest a close relation between photoassimilation of carbon and utilization of nitrogen.     

Modulation of the immunosuppressive effects of splenic macrophages in Fischer rats bearing adenocarcinoma 13762

Summary The nature of spleen cells in Fischer rats bearing a large size (>1 cm diameter) mammary adenocarcinoma 13762A (MAC) which block the immunostimulating capacities of MTP² (a synthetic immunomodulator) and suppress proliferation in vitro of splenic T and B lymphocytes by their respective mitogens was investigated. Splenic macrophages were recognized as the suppressor cells by (a) restoration of mitogenic responses by depletion of macrophages from spleen cell suspensions and (b) continued suppressor activity in spleen cell suspensions of tumor bearers devoid of viable T lymphocytes. Macrophage contact with T lymphocytes was required for the inhibition of T lymphocyte proliferation by concanavalin A as shown by (a) the absence of suppressor activity in supernatants derived from cultured suppressor macrophages, (b) lowering of the suppressor activity of intact macrophages after treatment with neuraminidase, (c) lowering of the suppressor activity of macrophages by addition of red cells to spleen cultures of tumor bearers indicating red cell interference with macrophage-T cell interaction and (d) lack of inhibiting action of suppressor macrophages on allogenic T lymphocyte proliferation showing macrophage T cell recognition for suppression.Animals bearing a large size tumor exhibited spleen hypertrophy and an increase in macrophage:lymphocyte ratio and a decrease in red cell:lymphocyte ratio. Splenic macrophages did not appear to be implicated in blocking antitumor immunity induction since (a) suppressor macrophages were absent in spleens during the inductive phase of the immune response and (b) MAC implanted in allogenic Wistar rats grew to about 2 cm diameter, induced splenic suppressor macrophages but the tumor was later rejected by the animals. Collectively the results suggest that suppressor macrophages are the result of increasing tumor volume rather than its cause.This study was supported by a grant from the National Cancer Institute of Canada Abbreviations used: Con A, Concanavalin A; LPS, lipopolysaccharide; PHA, phytohemagglutinin; MTP, maltose tetrapalmitate; MAC, mammary adenocarcinoma 13762; RPMI, Roswell Park Memorial Institute; TBR, tumor bearing rat; RBC, red blood cell     

Tetracyclines modulate cytosolic Ca2+ responses in the osteoclast associated with “Ca2+ receptor” activation

We report the effects of tetracycline analogues on cytosolic Ca²⁺ transients resulting from application of ionic nickel (Ni²⁺), a potent surrogate agonist of the osteoclast Ca²⁺ receptor. Preincubation with minocycline (1 mg/l) or a chemically modified tetracycline, 4-dedimethyl-aminotetracycline (CMT-1) (1 or 10 mg/l), resulted in a significant attenuation of the magnitude of the cytosolic [Ca²⁺] response to an application of 5 mM-[Ni²⁺]. Preincubation with doxycycline (1 or 10 mg/l) failed to produce similar results. In addition, application of minocycline alone (0.1–100 mg/l) resulted in a 3.5-fold elevation of cytosolic [Ca²⁺]. The results suggest a novel action of tetracyclines on the osteoclast Ca²⁺ receptor.     

Chemodiversity and α-Glucosidase Activity of Eucalyptus Species from Northwestern Himalaya,India

The aim of current work was to determine essential oils (EOs) composition from three Eucalyptus species, including E. citriodora, E. camaldulensis and E. globulus and assess their α-glucosidase inhibitory activity. The EOs were collected using the hydrodistillation technique and characterized by GC/MS, GC-FID and NMR. The isolated EOs from leaves parts of Eucalyptus species varied from 0.56 to 1.0 % on fresh weight basis. The content of the EOs was distinct according to the species. The most abundant metabolites were identified as citronellal (0–83.0 %), 1,8-cineole (0.2–44.8 %), spathulenol (0.4–16.1 %) α-pinene (0.4–15.9 %), p-cymene (3.7–11.9 %), citronellol (0–8.6 %), β-eudesmol (5.3–8.6 %) and β-pinene (0–7.1 %). The EOs obtained from targeted samples exhibited strong α-glucosidase inhibitory activity. These results are encouraging and underline that the EOs of Eucalyptus species may be a promising alternative source of natural antidiabetic.     

Studies on electrolyte-nonelectrolyte interactions: Viscosity behavior of alkali halides aqueous sucrose solutions

The effect of various added electrolytes (sodium and potassium halides of progressively increasing molecular volume) on the viscosity behavior of aqueous sucrose solution (292mM) has been investigated. Data are presented for the concentration range 0.125–3M of the electrolytes over the temperature range of 25 to 40°. The data have been found to satisfy Moulik's equation,(η/η₀)²M +K¹C², for concentrated solutions of electrolytes beyond the Einstein region. The “effective” rigid, molar volume (V_e) and apparent. Jones-Dole B-coefficient (in sucrose solution) have been computed by employing the Breslau-Miller treatment. The change in the viscosity behavior is attributed to structuring effects in solution.     

Studies on the viscosity behavior of alkali halides in aqueous D-xylose solution

The viscosity behavior of ternary systems comprising sodium or potassium halides (concentration range 0.125–3M in aqueous D-xylose solution (0.4M at 25, 30, 35, and 40° has been determined. It is found that Moulik's equation holds for such concentrated solutions beyond the Einstein region. Furthermore, the “effective” rigid molar volume and the apparent B coefficient have been computed from the relative viscosity data by employing the Breslau-Miller treatment. The results are explained in terms of the structure-making or -breaking effects in solution by analyzing the values of the apparent B coefficient obtained for different temperatures.